Bacterial vaginosis is associated with transcriptomic changes but not higher concentrations of cervical leukocytes in a study of women at high risk for HIV acquisition

Abstract

Background: The association between bacterial vaginosis (BV) and increased HIV acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix.

Methods: Participants (31 with BV and 30 with normal microbiota) underwent cervical biopsy at a single visit. Immune cells were quantified and sorted using flow cytometry (N=55), localization assessed by immunofluorescence (N=16), and function determined by bulk RNA sequencing (RNA-seq) of live CD45+ cells (N=21).

Results: Linear regression analyses demonstrated no differences in mean log2 [cells/mg tissue] between women with BV vs normal microbiota for antigen presenting cell (APC) subtypes linked to HIV risk (including CD1a+HLA-DR+ Langerhans cells, CD11c+CD14+ dendritic cells [DCs], and CD11c+HLA-DR+ DCs) and CD4+ T cells. Women with BV had a higher median proportion of CD11c+HLA-DR+ APCs (out of total cells) in cervical epithelium (0.1% vs 0.0%; p=0.03 using Mann-Whitney testing). RNA-seq identified 1,032 differentially expressed genes (adjusted p-value <0.05) in CD45+ cells between women with BV vs normal microbiota. Women with BV demonstrated downregulation of pathways linked to translation, metabolism, cell stress, and immune signaling.

Conclusions: BV alters immune cell localization and function; future studies are needed to address how these changes may mediate HIV acquisition risk.